Role of transforming growth factor-β1 in breast carcinogenesis

Abstract

The main objective of this presentation is to review current knowledge regarding molecular mechanisms of Transforming Growth Factor-β1(TGF-ß1) action in breast carcinogenesis. In addition, our recent results will be presented on TGF-ß1 gene polymorphism and its relationship to TGF-ß1 secretion in breast cancer (BC) patients. Special focus will be made on potential clinical applicability of TGF-ß1 as a putative diagnostic, prognostic or predictive tool in BC detection and treatment. TGF-ß1 has a complex multifunctional profile, with tumor suppressive effects in early stages of breast carcinogenesis, but progressive dominance of tumor promoting effects with transition to more advanced malignant states. Clarification of molecular mechanisms that control parallel processing of these opposing TGF-ß1 activities might suggest new approaches for shifting the balance in favor of net tumor suppression. Now, a major challenge remains in more precisely defining TGF-ß1 signaling pathways and their cancer-related alterations. Current dogma views human tumorigenesis as a molecular disruption of normal physiology through genetic, epigenetic, or somatic alterations. The genetic model offers biological plausibility to epidemiological studies that link the TGF-ß1 gene polymorphism, at codon 10 due to Leu10Pro substitution in the signal peptide, with the risk of developing BC. The somatic mutations approach, provides an explanation for the TGF-ß1 overexpression in advanced BC through mutations acquired in the components of Smad-mediated TGF-ß1 signaling pathway. The available results indicate decreased TßRII (TGF-ß1 receptor-type II) expression, rare TßRII gene mutations, but no mutations in Smad2 and Smad4 genes, in advanced BC patients. .

Keywords

• receptors
• transforming growth factor beta
• breast neoplasms
• tumor markers
• biological
• prognosis